Abstract:Inhaling a dangerous amount of nanoparticles leads to pulmonary inflammatory and immune disorders, which integrates several kinds of cells. Exosomes are suggested to play a crucial role in intercellular communication via miRNA transmission. To investigate the role of exosomal miRNA in nanoparticle phagocytosis, a total of 54 pneumoconiosis patients along with 100 healthy controls are recruited, exosomes derived from their venous blood are collected, and then exosomal miRNAs are profiled with high-throughput se… Show more
“…Compared to healthy controls, relative expression levels of exosomal let-7a-5p in venous blood from pneumoconiosis patients was decreased by 21.67% (0.47 ± 0.24 vs. 0.60 ± 0.24, t = 3.11, P = 0.002) (Fig. 1b ), consistent with high throughput sequencing results shown in our previous study [ 8 ], suggesting that exosomal let-7a-5p may be involved in the development of pneumoconiosis. Fig.…”
Section: Resultssupporting
confidence: 91%
“…Standard methods for exosome isolation and characterization have been previously described [ 8 ]. Briefly, five milliliters mixed serum was first diluted with 20-fold volume PBS and centrifuged at 2000 × g, 4 °C for 30 min.…”
Section: Methodsmentioning
confidence: 99%
“…For example, exosomal let-7a-5p and let-7i-5p were found to be associated with nanoparticle phagocytosis. Both of these factors simultaneously target WASL and VASP inducing inflammatory responses in lung tissue [ 8 ]. Moreover, let-7a was shown to be differentially expressed in different subtypes of non-small cell lung cancer [ 9 – 11 ].…”
BackgroundEither chronic or acute exposure to dust particles may lead to pneumoconiosis and lung cancer, and lung cancer mortality among patients diagnosed with pneumoconiosis is increasing. Utilizing genome-wide sequencing technology, this study aimed to identify methods to decrease the number of patients with pneumoconiosis who die from lung cancer.MethodsOne hundred fifty-four subjects were recruited, including 54 pneumoconiosis patients and 100 healthy controls. Exosomes were isolated from the venous blood of every subject. Distinctive miRNAs were identified using high throughput sequencing technology, and bioinformatics analysis predicted target genes involved in lung cancer as well as their corresponding biological functions. Moreover, cross-cancer alterations of genes related to lung cancer were investigated, and survival analysis was performed using 2437 samples with an average follow-up period of 49 months.ResultsLet-7a-5p was revealed to be downregulated by 21.67% in pneumoconiosis. Out of the 683 let-7a-5p target genes identified from bioinformatics analysis, four genes related to five signaling pathways were confirmed to be involved in lung cancer development. Alterations in these four target genes were then explored in 4105 lung cancer patients, and BCL2L1 and IGF1R were demonstrated to be aberrantly expressed. Survival analysis further revealed that high expression of BCL2L1 corresponded to reduced survival of lung cancer patients (HR (95%CI) = 1.75(1.33~2.30)), while patient survival time was unaffected by expression of IGF1R (HR (95%CI) = 1.15 (0.98~1.36)).ConclusionsIn patients with lung adenocarcinoma, simultaneous downregulation of exosomal let-7a-5p and elevated expression of BCL2L1 are useful as predictive biomarkers for poor survival.
“…Compared to healthy controls, relative expression levels of exosomal let-7a-5p in venous blood from pneumoconiosis patients was decreased by 21.67% (0.47 ± 0.24 vs. 0.60 ± 0.24, t = 3.11, P = 0.002) (Fig. 1b ), consistent with high throughput sequencing results shown in our previous study [ 8 ], suggesting that exosomal let-7a-5p may be involved in the development of pneumoconiosis. Fig.…”
Section: Resultssupporting
confidence: 91%
“…Standard methods for exosome isolation and characterization have been previously described [ 8 ]. Briefly, five milliliters mixed serum was first diluted with 20-fold volume PBS and centrifuged at 2000 × g, 4 °C for 30 min.…”
Section: Methodsmentioning
confidence: 99%
“…For example, exosomal let-7a-5p and let-7i-5p were found to be associated with nanoparticle phagocytosis. Both of these factors simultaneously target WASL and VASP inducing inflammatory responses in lung tissue [ 8 ]. Moreover, let-7a was shown to be differentially expressed in different subtypes of non-small cell lung cancer [ 9 – 11 ].…”
BackgroundEither chronic or acute exposure to dust particles may lead to pneumoconiosis and lung cancer, and lung cancer mortality among patients diagnosed with pneumoconiosis is increasing. Utilizing genome-wide sequencing technology, this study aimed to identify methods to decrease the number of patients with pneumoconiosis who die from lung cancer.MethodsOne hundred fifty-four subjects were recruited, including 54 pneumoconiosis patients and 100 healthy controls. Exosomes were isolated from the venous blood of every subject. Distinctive miRNAs were identified using high throughput sequencing technology, and bioinformatics analysis predicted target genes involved in lung cancer as well as their corresponding biological functions. Moreover, cross-cancer alterations of genes related to lung cancer were investigated, and survival analysis was performed using 2437 samples with an average follow-up period of 49 months.ResultsLet-7a-5p was revealed to be downregulated by 21.67% in pneumoconiosis. Out of the 683 let-7a-5p target genes identified from bioinformatics analysis, four genes related to five signaling pathways were confirmed to be involved in lung cancer development. Alterations in these four target genes were then explored in 4105 lung cancer patients, and BCL2L1 and IGF1R were demonstrated to be aberrantly expressed. Survival analysis further revealed that high expression of BCL2L1 corresponded to reduced survival of lung cancer patients (HR (95%CI) = 1.75(1.33~2.30)), while patient survival time was unaffected by expression of IGF1R (HR (95%CI) = 1.15 (0.98~1.36)).ConclusionsIn patients with lung adenocarcinoma, simultaneous downregulation of exosomal let-7a-5p and elevated expression of BCL2L1 are useful as predictive biomarkers for poor survival.
“…Exosomes consist of proteins, mRNA, and noncoding miRNA surrounded by a lipid bilayer membrane. [10][11][12][13] Further RNA forms including transfer RNA, ribosomal RNA, nucleolar RNA, and long noncoding RNA (lncRNA) have also been identified in exosomes. 14 Topical studies have demonstrated that fragments of DNA may exist in exosomes as well.…”
Mesenchymal stem cells (MSCs) are multipotent stromal cells present in various adult tissues. Several studies suggest that MSCs secrete exosomes that perform as mediators in the tumor niche and play several roles in tumorigenesis, angiogenesis, and metastasis. In contrast, there are other studies supporting the tumor-suppressing effects of MSC-derived exosomes. Therefore, the exact association of MSC exosomes and tumor cells remains open to debate. This review aimed to demonstrate the present knowledge of MSC-derived exosomes in cancer research and to illustrate current approaches to make use of modified exosomes as a platform in therapeutic strategies in cancer.
“…For example, a recent study found that silica nanoparticle exposure‐induced inflammation and activated autophagy, which eventually lead to endothelial dysfunction in silicosis . For macrophages that were exposed to silica dust, it was suggested that MCPIP1 induced autophagy through the p53 signaling pathway, which could lead to cellular apoptosis and trigger the proliferation and trans‐differentiation of pulmonary fibroblast . Alternatively, several studies suggested that autophagy deficiency could aggravate lung damage …”
Increased deposition of silica dust in pulmonary interstitial tissues leads to silicosis, in which autophagy plays a defensive role in silica dust-associated stress response and cell death. Our previous studies revealed that silica dust exposure contributed to autophagy in pulmonary macrophages in vivo, while the specific regulatory mechanism is still unclear. This study aimed to figure out the regulatory mechanism as well as the role of autophagy in the pathogenesis of experimental silicosis. We used 3-methyladenine (3-MA) and ABT-737 to suppress the expression of phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and B cell leukemia/lymphoma 2 (Bcl-2), two critical initiators of autophagy, and detected and evaluated the autophagy in NR8383 cells with or without silica dust exposure. We found that exposure of silica dust increased autophagy in NR8383 cells and elevated the expression of Beclin1 and PIK3C3, but it reduced the expression of Bcl-2. The relationship among Beclin1, PIK3C3, and Bcl-2 were then investigated using immunoprecipitation analysis, and we found that suppression of PIK3C3 and/or Bcl-2 using 3-MA and/or ABT-737 could alter the autophagy induced by silica dust in NR8383 cells, and the complexes of Beclin1/PIK3C3 and Beclin1/Bcl-2 were both downregulated, which may be that inhibition of PIK3C3 and Bcl-2 altered the affinity of Beclin1 with PIK3C3 and Bcl-2 and lead to the silence of PIK3C3 signaling. These findings indicate that silica dust exposure induces autophagy via changing the connectivity of Beclin1 from Bcl-2 to PIK3C3.
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